Mechanism And Clinical Prognosis Analysis Of Nicotinamide N-methyltransferase In The Development And Progression Of Pancreatic Cancer

Objective:Chronic pancreatitis is one of the etiology of some patients with pancreatic cancer.In the presence of calcification in the lesion,it is very difficult to diagnose pancreatic cancer from patients with chronic pancreatitis.In this study,we investigate the expression of NNMT gene in chronic pancreatitis and pancreatic cancer.According to the association between expression of NNMT gene in pancreatic cancer tissues with the size of cancer tissue,age of patients,stage of cancer development,prognosis and CA19-9 expression.we discuss whether the molecule may be a new target molecule for the differentiation of chronic pancreatitis and pancreatic cancer,and explore the prognostic significance of NNMT gene in pancreatic cancer patients.METHODS:The expression of NNMT gene in 267 patients treated with NNMT was detected by immunohistochemistry.Explore the association between expression of NNMT gene in pancreatic cancer tissues with the size of cancer tissue,the age of patients and the stage of cancer development.Follow-up analysis of NNMT gene expression levels and other clinical features and pancreatic cancer patients were analyzed to explore the prognostic value of NNMT gene in pancreatic cancer patients.Human pancreatic cancer cell lines SW1990,CAPAN1,BXPC3,ASPC1,CAPAN2 and PATU8988T were used to down-regulate the expression of NNMT in human pancreatic cancer cell lines by siRNA.The effects of NNMT expression on the growth and apoptosis of pancreatic cancer cells influences.Result:In 178 cases of pancreatic cancer,99 cases of high expression of NNMT,high expression rate of 55.6%;28 cases of 28 cases of chronic pancreatitis specimens,4 specimens of NNMT gene expression,high expression rate of 14.8%;61 There were 16 cases of NNMT overexpression,the high expression rate was 21.4%.The high expression rate of NNMT gene in pancreatic cancer was significantly higher than that in adjacent tissues(21.4%)and chronic pancreatitis(14.8%)(p<0.001).The high expression rate of NNMT(45.8%)p = 0.014;the high expression rate of NNMT with tumor diameter(cm)greater than or equal to 4 was 71.8%higher than that of tumor diameter(P<0.05),and the high expression rate of NNMT was 64.2%(44.9%)p<0.001.The high expression rate of NNMT in advanced TNM patients was 78.2%higher than that in early stage of TNM staging(45.5%)p<0.001;tumor The high expression rate of NNMT was 59.2%and 60.3%in patients with moderate and low differentiation,and the higher expression rate of NNMT(17.6%)p = 0.004 in patients with highly differentiated tumor.The high expression level of CA19-9(>34U/ml)The expression rate was 64.4%higher than the CA19-9 low expression level(<34U/ml)in patients with high NNMT expression(43.2%)p = 0.005.The median OS of patients with NNMTh and NNMT1 was 7.0 months(95%CI:5.275-8.725)and 11.5 months(95%CI:9.759-13.241)(p = 0.005).In addition to NNMT expression levels,other factors affected the univariate analysis of OS median values including age(p = 0.011),tumor diameter(p = 0.027),nervous system involvement(p = 0.033),TNM staging(p = 0.001),distant(P<0.001)and tumor differentiation(p = 0.021).(HR:0.651;95%CI:0.421-0.947;p = 0.041),but there was no significant difference between the two groups(P<0.05),but there was no significant difference between the two groups(P<0.05),NNMT1(hazard ratio[HR]:0.399;95%CI:0.284-0.560;(HR:0.506;95%CI:0.299-0.719;p = 0.015)and highly tumor differentiation(HR:0.592;95%CI:0.319-0.894.P = 0.044)were benign prognostic factors;NNMTh,Nervous system involvement,TNM stage ? or ? and poorly differentiated tumors for poor prognosis.Pancreatic carcinoma cell line CAPANl with higher expression of NNMT gene were selected in follow up experiment.According to RT-PCR and western bloting,we found that compared with the control group,the expression of NNMT was significantly lower than the control group(P<0.05).The cell viability of the cells treated with siRNA was significantly lower than that of the control group.The apoptotic rate of MTT assay siRNA was significantly higher than that of the control group Control group.Conclusion:NNMTh is significantly associated with apoptotic activity of pancreatic cancer cells.These results suggest that NNMTh and NNMT1 tend to be associated with poor clinical pathology in patients with pancreatic cancer.Compared with the expression of NNMT gene in pancreatic cancer tissues and chronic pancreatitis tissues and adjacent tissues,the high expression rate of NNMT gene in adenocarcinoma tissue was significantly higher than that in adjacent tissues and chronic pancreatitis tissues.Under the effective validation and rational use,NNMT gene expression may be a target molecule for distinguishing chronic pancreatitis from pancreatic cancer.(P<0.001),low differentiation level(p = 0.004),and high expression level of CA19-9(p(p<0.001),higher tumor volume(p<0.001),higher TNM staging = 0.005)was significantly correlated.These results suggest that NNMTh and NNMT1 tend to be associated with poor clinical pathology in patients with pancreatic cancer.NNMT high expression can be seen as a poor prognosis,such patients may have a shorter survival.NNMTh has the potential to become a potential prognostic marker.